Epivir

The following dosing information is available for EPIVIR (lamivudine):

Dosing
Administration
EPIVIR
LAMIVUDINE

The usual dosage of lamivudine for the treatment of HIV-1 infection in adults is 150 mg twice daily or 300 mg once daily.

When lamivudine oral solution containing 10 mg/mL is used for the treatment of HIV-1 infection in pediatric patients 3 months of age or older, the recommended dosage is 5 mg/kg twice daily or 10 mg/kg once daily (up to 300 mg maximum daily dosage). Consider HIV-1 viral load and CD4+ cell count/percentage when selecting the dosing interval for patients initiating treatment with oral solution.

When lamivudine 150-mg scored tablets are used in pediatric patients 3 months of age or older who weigh 14 kg or more and are able to swallow tablets, the recommended dosage is based on weight (see Table 1and Table 2). Data regarding efficacy of the once-daily regimen of lamivudine given as 150-mg scored tablets in pediatric patients 3 months of age or older is limited to those who transitioned from a twice-daily regimen to a once-daily regimen after 36 weeks of treatment.

Table 1. Twice-daily Lamivudine for Treatment of HIV-1 Infection in Pediatric Patients Weighing at least 14 kg (150-mg Tablets)

Weight (kg) AM Dose PM Dose 14 to <20 75 mg (half of 150-mg 75 mg (half of 150-mg tablet) tablet) 20 to <25 75 mg (half of 150-mg 150 mg (one 150-mg tablet) tablet) >=25 150 mg (one 150-mg 150 mg (one 150-mg tablet) tablet)

Table 2. Once-daily Lamivudine for Treatment of HIV-1 Infection in Pediatric Patients Weighing at least 14 kg (150-mg Tablets)

Weight (kg) Once-daily Dose 14 to <20 150 mg (one 150-mg tablet) 20 to <25 225 mg (one and one-half 150-mg tablets) >=25 300 mg (two 150-mg tablets or one 300-mg tablet)

Although safety and efficacy of lamivudine in infants younger than 3 months of age have not been established, some experts suggest that neonates younger than 4 weeks of age+ can receive lamivudine in a dosage of 2 mg/kg twice daily and infants 4 weeks of age or older+ can receive a dosage of 4 mg/kg (up to 150 mg) twice daily.

When empiric HIV therapy+ is used for prevention of perinatal HIV transmission + in neonates at highest risk of HIV acquisition, a 3-drug antiretroviral regimen of zidovudine, lamivudine, and nevirapine is recommended and should be initiated as soon as possible after birth (within 6-12 hours).

For empiric HIV therapy+ in HIV-exposed neonates, experts recommend that lamivudine be given in a dosage of 2 mg/kg twice daily from birth to 4 weeks of age followed by 4 mg/kg twice daily from 4-6 weeks of age.

The optimal duration of empiric HIV therapy+ in HIV-exposed neonates at highest risk of HIV acquisition is unknown. Many experts recommend that the 3-drug regimen be continued for 6 weeks; others discontinue nevirapine and/or lamivudine if the result of the neonate's HIV nucleic acid amplification test (NAAT) is negative, but recommend continuing zidovudine for 6 weeks.

Clinicians can consult the National Perinatal HIV Hotline at 888-448-8765 for information regarding selection of antiretrovirals, including dosage considerations, for the prevention of perinatal HIV transmission.

When lamivudine (100-mg tablets or oral solution containing 5 mg/mL) is used for the treatment of chronic HBV infection in adults, the recommended dosage is 100 mg once daily.

The recommended oral dosage of lamivudine for the treatment of chronic HBV infection in pediatric patients 2-17 years of age is 3 mg/kg once daily up to a maximum daily dosage of 100 mg. The oral solution formulation should be prescribed for patients requiring a dosage less than 100 mg or unable to swallow tablets.

Lamivudine is administered orally once or twice daily without regard to meals. For the treatment of HIV-1 infection, lamivudine is commercially available as an oral solution containing 10 mg/mL or tablets containing 150 or 300 mg of the drug (Epivir(R), generic). The 150-mg scored tablets are the preferred preparation in pediatric patients who weigh 14 kg or more and can swallow tablets.

The oral solution should be used in those unable to safely and reliably swallow tablets. Lamivudine is used in conjunction with other antiretrovirals for the treatment of HIV-1 infection. For the treatment of chronic HBV infection, lamivudine is commercially available as an oral solution containing 5 mg/mL or film-coated tablets containing 100 mg of the drug (Epivir-HBV(R), generic).

The 5-mg/mL oral solution should be used in patients requiring a dosage less than 100 mg and in children unable to reliably swallow tablets. Lamivudine preparations labeled by FDA for treatment of chronic HBV infection should not be used in HIV-infected patients because they contain a lower dosage of the drug than that required for treatment of HIV-1 infection. If such preparations are used for the management of chronic HBV infection in a patient with unrecognized or untreated HIV infection, rapid emergence of HIV resistance is likely to result because of the subtherapeutic dose and the inappropriateness of monotherapy for HIV-infected individuals.

Store lamivudine 100-mg, 150-mg, and 300-mg tablets at 25degreesC (excursions permitted between 15-30degreesC). Store lamivudine 5-mg/mL oral solution at 20-25degreesC and store lamivudine 10-mg/mL oral solution at 25degreesC.

Dosing information for EPIVIR
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
EPIVIR 150 MG TABLET	Maintenance	Adults take 1 tablet (150 mg) by oral route every 12 hours
EPIVIR 300 MG TABLET	Maintenance	Adults take 1 tablet (300 mg) by oral route once daily
EPIVIR 10 MG/ML ORAL SOLN	Maintenance	Adults take 15 milliliters (150 mg) by oral route every 12 hours

Generic dosing information for LAMIVUDINE
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
LAMIVUDINE 150 MG TABLET	Maintenance	Adults take 1 tablet (150 mg) by oral route every 12 hours
LAMIVUDINE 10 MG/ML ORAL SOLN	Maintenance	Adults take 15 milliliters (150 mg) by oral route every 12 hours
LAMIVUDINE 300 MG TABLET	Maintenance	Adults take 1 tablet (300 mg) by oral route once daily
LAMIVUDINE 300 MG/30ML SOL CUP	Maintenance	Adults take 15 milliliters (150 mg) by oral route every 12 hours

The following drug interaction information is available for EPIVIR (lamivudine):

Contraindicated
Severe
Moderate

There are 0 contraindications.

There are 6 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Deoxycytidine Kinase Substrates/Cladribine SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Clofarabine, cytarabine, emtricitabine, fludarabine, gemcitabine, lamivudine, molnupiravir, nelarabine and zalcitabine may inhibit the intracellular phosphorylation of cladribine by deoxycytidine kinase (dCK). CLINICAL EFFECTS: Concurrent administration of clofarabine, cytarabine, emtricitabine, fludarabine, gemcitabine, lamivudine, molnupiravir, nelarabine, or zalcitabine with cladribine may result in decreased clinical efficacy of cladribine. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of lamivudine states that the concurrent use of lamivudine and cladribine is not recommended.(1) The manufacturer of cladribine states that concurrent use of compounds that require activation by intracellular phosphorylation should be avoided.(2) DISCUSSION: Cladribine undergoes a series of phosphorylations to its active metabolites. In a case report, a patient on lamivudine who received cladribine concurrently did not experience a decrease in his lymphocyte count. After discontinuation of lamivudine and readministration of cladribine, his lymphocytes dropped as expected.(3) It is expected that other compounds phosphorylated by dCK would also decrease cladribine's efficacy.(4) Compounds phosphorylated by dCK include: clofarabine, cytarabine, emtricitabine, fludarabine, gemcitabine, lamivudine, molnupiravir, nelarabine and zalcitabine.	CLADRIBINE, MAVENCLAD
Sorbitol/Lamivudine SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Sorbitol increases the osmotic pressure in the intestine, resulting in accelerated small intestinal transit time and decreased absorption and bioavailability of lamivudine. CLINICAL EFFECTS: Concurrent administration of sorbitol and lamivudine may result in decreased clinical efficacy of lamivudine.(1) Reduction in lamivudine exposure is sorbitol dose-dependent. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of lamivudine states that the concurrent use of lamivudine and sorbitol should be avoided.(1) Consider more frequent monitoring of HBV viral load when chronic coadministration cannot be avoided. DISCUSSION: In an open label, randomized sequence, 4-period, crossover trial in 16 healthy adults, coadministration of a single dose of lamivudine (300 mg) with sorbitol (3.2 grams) resulted in a dose-dependent decrease of lamivudine's area-under-the-curve (AUC(0-24), AUC infinity) and maximum concentration (Cmax) of 20%, 28%, and 28%. A single dose of lamivudine with sorbitol (10.2 grams) resulted in a decrease of lamivudine's AUC and Cmax of 39%, 52%, and 52%. A single dose of lamivudine with sorbitol (13.4 grams) resulted in a decrease of lamivudine's AUC and Cmax of 36%, 55%, and 55%.(1)	KIONEX, SPS
Betibeglogene Autotemcel/Anti-Retrovirals; Hydroxyurea SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Betibeglogene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. Hydroxyurea may interfere with hematopoietic stem cell (HSC) mobilization of CD34+ cells.(1) CLINICAL EFFECTS: Use of hydroxyurea before mobilization may result in unsuccessful stem cell mobilization. Use of antiretrovirals before mobilization and apheresis may interfere with the production of betibeglogene autotemcel. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discontinue antiretrovirals and hydroxyurea for at least one month prior to mobilization and until all cycles of apheresis are completed. If a patient requires antiretrovirals for HIV prophylaxis, then confirm a negative HIV test before beginning mobilization and apheresis of CD34+ cells. DISCUSSION: Antiretroviral medications and hydroxyurea may interfere with the manufacturing of betibeglogene autotemcel therapy.(1)	ZYNTEGLO
Elivaldogene Autotemcel/Anti-Retrovirals SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Elivaldogene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of elivaldogene autotemcel. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discontinue antiretrovirals for at least one month prior to mobilization and until all cycles of apheresis are completed. If a patient requires antiretrovirals for HIV prophylaxis, then confirm a negative HIV test before beginning mobilization and apheresis of CD34+ cells. DISCUSSION: Antiretroviral medications may interfere with the manufacturing of elivaldogene autotemcel therapy.(1)	SKYSONA
Lovotibeglogene Autotemcel/Anti-Retrovirals SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Lovotibeglogene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of lovotibeglogene autotemcel.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discontinue antiretrovirals for at least one month prior to mobilization and until all cycles of apheresis are completed.(1) There are some long-acting antiretroviral medications that may require a longer duration of discontinuation for elimination of the medication. If a patient is taking anti-retrovirals for HIV prophylaxis, confirm a negative test for HIV before beginning mobilization and apheresis of CD34+ cells.(1) DISCUSSION: Antiretroviral medications may interfere with the manufacturing of lovotibeglogene autotemcel therapy.(1)	LYFGENIA
Atidarsagene Autotemcel/Anti-Retrovirals SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Atidarsagene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of atidarsagene autotemcel. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discontinue antiretrovirals for at least one month prior to mobilization (or the expected duration of time needed for elimination of the medication) until all cycles of apheresis are completed. If a patient requires antiretrovirals for HIV prophylaxis, then confirm a negative HIV test before beginning mobilization and apheresis of CD34+ cells. DISCUSSION: Antiretroviral medications may interfere with the manufacturing of atidarsagene autotemcel therapy.(1)	LENMELDY

There are 0 moderate interactions.

The following contraindication information is available for EPIVIR (lamivudine):

Overview
Contraindicated
Severe
Moderate

Drug contraindication overview.

*Previous hypersensitivity to lamivudine.

There are 4 contraindications. Absolute contraindication.

Contraindication List
Acute pancreatitis
Chronic pancreatitis
Lactation
Lactic acidosis

There are 4 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
Chronic kidney disease stage 5 (failure) GFr<15 ml/min

There are 1 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Kidney disease with likely reduction in glomerular filtration rate (GFr)

The following adverse reaction information is available for EPIVIR (lamivudine):

Overview
Severe
Less Severe

Adverse reaction overview.

In the treatment of HIV infection in adults, the most common reported adverse reactions (incidence >=15%) were headache, nausea, malaise and fatigue, nasal signs and symptoms, diarrhea, and cough. In the treatment of HIV infection in pediatric patients, the most common reported adverse reactions (incidence >=15%) were fever and cough. In the treatment of HBV infection, the most common reported adverse reactions (incidence >=10% and reported at a rate greater than placebo) were ear, nose, and throat infections; sore throat; and diarrhea.

There are 14 severe adverse reactions.

More Frequent	Less Frequent
Elevated serum lipase Paresthesia	Neutropenic disorder Thrombocytopenic disorder

Rare/Very Rare
Abnormal hepatic function tests Anaphylaxis Anemia Lactic acidosis Lymphadenopathy Pancreatitis Pure red cell aplasia Rhabdomyolysis Splenomegaly Steatosis of liver

There are 32 less severe adverse reactions.

More Frequent	Less Frequent
Cough Diarrhea Fatigue Fever Headache disorder Infection of ear Malaise Nausea Peripheral neuropathy Sore throat	Abdominal pain with cramps Anorexia Arthralgia Chills Depression Dizziness Dyspepsia Hyperlipidemia Insomnia Myalgia Rhinitis Vomiting

Rare/Very Rare
Alopecia Cramps General weakness Hyperglycemia Muscle weakness Pruritus of skin Skin rash Stomatitis Urticaria Wheezing

The following precautions are available for EPIVIR (lamivudine):

Pediatric
Pregnant
Lactation
Geriatric

The safety and efficacy of lamivudine for the treatment of HIV-1 (Epivir(R)) have been established in pediatric patients 3 months of age and older. The scored tablet is the preferred formulation for HIV-1-infected pediatric patients weighing at least 14 kg for whom a solid dosage form is appropriate; in the ARROW trial, pediatric patients who received the oral solution had lower rates of virologic suppression, lower plasma lamivudine exposure, and developed viral resistance more frequently. The safety and efficacy of lamivudine for the treatment of chronic HBV (Epivir-HBV(R)) in pediatric patients younger than 2 years of age have not been established.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

Lamivudine crosses the placenta and is distributed into cord blood in concentrations similar to maternal serum concentrations. To monitor maternal-fetal outcomes of pregnant women exposed to antiretroviral agents, including lamivudine, the Antiretroviral Pregnancy Registry was established. Clinicians are encouraged to contact the registry at 800-258-4263 or https://www.apregistry.com/

to report cases of prenatal exposure to antiretroviral agents. Data from the Antiretroviral Pregnancy Registry show no difference in the risk of overall major birth defects for lamivudine compared with the background rate for major birth defects in the US reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP). Reproduction studies in rats or rabbits using oral lamivudine dosages that resulted in plasma concentrations up to approximately 35 times higher than plasma concentrations attained with the recommended human dosage used for the treatment of HIV infection in adults have not revealed evidence of teratogenicity. Although there was evidence of early embryolethality in rabbits at exposure levels similar to those observed in humans, this effect was not seen in rats at exposure levels up to 35 times higher than those in humans.

Lamivudine is distributed into milk in humans. It is not known whether the drug affects human milk production or affects the breast-fed infant. The HHS perinatal HIV transmission guideline provides updated recommendations on infant feeding.

The guideline states that patients with HIV should receive evidence-based, patient-centered counseling to support shared decision making about infant feeding. During counseling, patients should be informed that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates the risk of postnatal HIV transmission to the infant. Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces the risk of breastfeeding HIV transmission to <1%, but does not completely eliminate the risk.

Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery. If lamivudine is being used for treatment of chronic HBV infection, the benefits of breast-feeding and the importance of lamivudine to the woman should be considered along with the potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.

Clinical trials of lamivudine (Epivir(R) and Epivir-HBV(R)) did not include sufficient numbers of patients 65 years of age or older to determine whether they respond differently from younger subjects. Use caution when administering lamivudine to geriatric patients, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

HIV infection
B20	Human immunodeficiency virus [HIv] disease
B97.35	Human immunodeficiency virus, type 2 [HIV 2] as the cause of diseases classified elsewhere
O98.7	Human immunodeficiency virus [HIv] disease complicating pregnancy, childbirth and the puerperium
O98.71	Human immunodeficiency virus [HIv] disease complicating pregnancy
O98.711	Human immunodeficiency virus [HIv] disease complicating pregnancy, first trimester
O98.712	Human immunodeficiency virus [HIv] disease complicating pregnancy, second trimester
O98.713	Human immunodeficiency virus [HIv] disease complicating pregnancy, third trimester
O98.719	Human immunodeficiency virus [HIv] disease complicating pregnancy, unspecified trimester
O98.72	Human immunodeficiency virus [HIv] disease complicating childbirth
O98.73	Human immunodeficiency virus [HIv] disease complicating the puerperium
Z21	Asymptomatic human immunodeficiency virus [HIv] infection status